View source for 2vn1


==Crystal structure of the FK506-binding domain of Plasmodium falciparum FKBP35 in complex with FK506==
<StructureSection load='2vn1' size='340' side='right'caption='[[2vn1]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2vn1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Plasmodium_falciparum_3D7 Plasmodium falciparum 3D7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VN1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VN1 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FK5:8-DEETHYL-8-[BUT-3-ENYL]-ASCOMYCIN'>FK5</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vn1 OCA], [https://pdbe.org/2vn1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vn1 RCSB], [https://www.ebi.ac.uk/pdbsum/2vn1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vn1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FKB35_PLAF7 FKB35_PLAF7] Has peptidylprolyl isomerase (PPIase) and co-chaperone activities (PubMed:15664653, PubMed:15850699). Assists protein folding by catalyzing the peptidyl conversion of cis and trans rotamers of the prolyl amide bond of protein substrates (PubMed:15664653, PubMed:15850699, PubMed:23974147). Inhibits calcineurin phosphatase activity in vitro (PubMed:15850699, PubMed:17289400, PubMed:23974147). Plays an essential role in merozoite egress from host erythrocytes (PubMed:15664653, PubMed:23974147).<ref>PMID:15664653</ref> <ref>PMID:15850699</ref> <ref>PMID:17289400</ref> <ref>PMID:23974147</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vn/2vn1_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vn1 ConSurf].
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== Publication Abstract from PubMed ==
The emergence of multi-drug-resistant strains of Plasmodium parasites has prompted the search for alternative therapeutic strategies for combating malaria. One possible strategy is to exploit existing drugs as lead compounds. FK506 is currently used in the clinic for preventing transplant rejection. It binds to a alpha/beta protein module of approximately 120 amino acids known as the FK506 binding domain (FKBD), which is found in various organisms, including human, yeast, and Plasmodium falciparum (PfFKBD). Antiparasitic effects of FK506 and its analogues devoid of immunosuppressive activities have been demonstrated. We report here the crystallographic structure at 2.35 A resolution of PfFKBD complexed with FK506. Compared to the human FKBP12-FK506 complex reported earlier, the structure reveals structural differences in the beta5-beta6 segment that lines the FK506 binding site. The presence in PfFKBD of Cys-106 and Ser-109 (substituting for His-87 and Ile-90, respectively, in human FKBP12), which are 4-5 A from the nearest atom of the FK506 compound, suggests possible routes for the rational design of analogues of FK506 with specific antiparasitic activity. Upon ligand binding, several conformational changes occur in PfFKBD, including aromatic residues that shape the FK506 binding pocket as shown by NMR studies. A microarray analysis suggests that FK506 and cyclosporine A (CsA) might inhibit parasite development by interfering with the same signaling pathways.

Crystal Structure of the FK506 Binding Domain of Plasmodium falciparum FKBP35 in Complex with FK506.,Kotaka M, Ye H, Alag R, Hu G, Bozdech Z, Preiser PR, Yoon HS, Lescar J Biochemistry. 2008 May 9;. PMID:18465874<ref>PMID:18465874</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2vn1" style="background-color:#fffaf0;"></div>

==See Also==
*[[FKBP 3D structures|FKBP 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Plasmodium falciparum 3D7]]
[[Category: Alag R]]
[[Category: Kotaka M]]
[[Category: Lescar J]]
[[Category: Preiser PR]]
[[Category: Ye H]]
[[Category: Yoon HS]]